The present invention relates to a novel one-pot process for the preparation of 7-amino-3-exomethylene-3-cepham-4-carboxylic acid ester hydrochloride (II) by deoxygenation and deacylation of the side chain of 7-acylamino-3-exomethylene-3-cepham-1-oxide-4-carboxylic acid ester (I).
7-acylamino-3-exomethylene-3-cepham-1-oxide-4-carboxylic acid ester (I) and 7-amino-3-exomethylene-3-cepham-4-carboxylic acid ester hydrochloride (II) are important intermediates in some reaction schemes for the manufacture of clinically useful antibacterial agents, such as Cefaclor (7-D-phenylglycylamido-3-chloro-3-cephem-4-carboxylic acid).
A previously known method, for converting 7-acylamino-3-exomethylene-3-cepham-1-oxide-4-carboxylic acid ester (I) into 7-amino-3-exomethylene-3-cepham-4-carboxylic acid ester (II) requires two steps and the overall yield is low. These steps are: 1) deoxygenation of 3-exomethylene sulfoxide (I) by treatment with phosphorous trichloride in DMF [see ref.: "Recent Advances in Chemistry of Beta-lactam Antibiotics," special publication No. 28, page 107 (1976)], and 2) deacylation by treating the isolated sulphide (III) with phosphorous pentachloride and pyridine followed by the addition of anhydrous alcohol (methanol, isobutanol, etc.) to give the desired 7-amino-3-exomethylene (II) [see ref.: J. Org. Chem., 38, 2995 (1973)].
The prior art two-step reaction scheme is illustrated below showing the production and isolation of the intermediate sulphide (III): ##STR1##